P976: REAL-WORLD OUTCOMES OF PATIENTS WITH PENTA-EXPOSED MULTIPLE MYELOMA WHO WERE TREATED WITH SELINEXOR AND DEXAMETHASONE: KOREAN MULTICENTER RETROSPECTIVE ANALYSIS
Authors: Jun Ho Yi, Sung-Soo Park, Chang-Ki Min, Hyeon-Seok Eom, Youngil Koh, Ja Min Byun, Sung-Soo Yoon, Jae Hoon Lee, Sung-Hoon Jung, Je-Jung Lee, Sang Eun Yoon, Kihyun Kim
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: The outcomes of patients with myeloma after exposed to penta-classes (2 or more proteasome inhibitor(PI)s, immunomodulatory drug(IMiD)s, and 1 anti-CD38 antibody) are extremely poor. Selinexor is the first in class, exportin inhibitor, approved for those patients, but intractable toxicities may limit its use. Aims: To provide real-world efficacy and safety of the combination, we carried out a retrospective analysis of patients with relapsed or refractory multiple myeloma who were treated with selinexor/dexamethasone (XD) in Korea. Methods: From November 2020 to October 2022, 48 patients who were treated with XD in 7 tertiary institutes were included in the analysis. We collected characteristics including age, sex, MM features (high-risk cytogenetics by fluorescence in situ hybridization, subtype, anti-myeloma treatment, and SCT status), and survival data. The need for informed consent was waived by the institutional review boards of the respective sites. This study was carried out by the Korean Multiple Myeloma Working Party (KMM-2107 study). Results: Their median age was 64 (range, 44 - 87), and 26 (54.2%) patients were male. With the median prior line of therapy of 6 (range, 4 - 16), 29 (60.4%), 20 (41.7%), and 20 (41.7%) were refractory to IMiD, PI, and daratumumab, respectively. Thirty-three (68.7%) and three (6.3%) patients received autoSCT and alloSCT, respectively. No patient was exposed to anti-BCMA agents. Starting dose were 80mg twice/wk in 39 patients, 60 mg twice/wk in 5 patients, and 100 mg/wk in 4 patients. With the median duration of therapy was 39 days (95% CI, 20.2 – 57.8), progressive disease (n=31) was the dominant cause of treatment discontinuation followed by severe adverse events (n=15), non-compliance (n=2). ORR was 25% (1 VGPR and 11 PRs, 95% CI 15.3 – 40.8), and median time to response was 0.9 months (95% CI, 0.7 – 1.0). The median PFS was 2.1 months (95% CI, 1.7 – 2.5) and the median duration of response was 3.2 months (95% CI, 0.8 – 5.6). Patients who started at a standard dose (80mg twice/wk) showed a trend for worse PFS compared to patients who started at reduced doses (2.1 vs. 5.2, p = 0.052, Figure). In addition, patients who had experienced delay of treatment (1.9 vs. 3.0, p = 0.006), and dose reduction (1.7 vs. 2.7, p = 0.016) showed better PFS. After failure to XD treatment, 17 patient received subsequent therapy, whose PFS was 2.4 months (95% CI, 1.1 – 3.6, Figure). The median OS was 4.6 months (95% CI, 2.3 – 6.9). Among 46 patients in whom adverse events were documented, the incidence of grade 3~4 hematologic toxicities were as follows; neutropenia (25, 54.3%), anemia (28, 60.9%), thrombocytopenia (39, 84.8%), and febrile neutropenia (13, 28.3%). Twelve (25.0%) patients experienced dose reduction due to thrombocytopenia (n=5), nausea/vomiting (n=4), and general weakness (n=3). And a delay of treatment was required in 17 (35.4%) patients with a median duration of 15 days (bone marrow suppression 10, infection 3, fatigue 2, nausea/vomiting 2). Summary/Conclusion: The efficacy of XD treatment in heavily pretreated patients was modest. Improving treatment adherence through reduction of starting dose or delaying treatment, may result in better outcomes.Keywords: Multiple myeloma